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WO1997032872A1 - Composes comportant un groupe sulfamate - Google Patents

Composes comportant un groupe sulfamate Download PDF

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Publication number
WO1997032872A1
WO1997032872A1 PCT/GB1997/000600 GB9700600W WO9732872A1 WO 1997032872 A1 WO1997032872 A1 WO 1997032872A1 GB 9700600 W GB9700600 W GB 9700600W WO 9732872 A1 WO9732872 A1 WO 9732872A1
Authority
WO
WIPO (PCT)
Prior art keywords
ring
compound
strucmre
compound according
sulphamate
Prior art date
Application number
PCT/GB1997/000600
Other languages
English (en)
Inventor
Michael John Reed
Barry Victor Lloyd Potter
Original Assignee
Imperial College Of Science Technology And Medicine
University Of Bath
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from GBGB9604709.7A external-priority patent/GB9604709D0/en
Priority to US09/142,194 priority Critical patent/US6083978A/en
Priority to AT97905332T priority patent/ATE286038T1/de
Priority to DE69732098T priority patent/DE69732098T2/de
Priority to AU22255/97A priority patent/AU2225597A/en
Priority to JP9531567A priority patent/JP2000506161A/ja
Priority to EP97905332A priority patent/EP0885211B1/fr
Application filed by Imperial College Of Science Technology And Medicine, University Of Bath filed Critical Imperial College Of Science Technology And Medicine
Publication of WO1997032872A1 publication Critical patent/WO1997032872A1/fr
Priority to US09/193,970 priority patent/US6476011B1/en
Priority to US09/238,345 priority patent/US6187766B1/en
Priority to US09/579,163 priority patent/US6642397B1/en
Priority to US09/638,315 priority patent/US6506792B1/en
Priority to US09/794,853 priority patent/US6903084B2/en
Priority to US10/082,007 priority patent/US6677325B2/en
Priority to US10/084,235 priority patent/US7098199B2/en
Priority to US10/327,500 priority patent/US7129269B2/en
Priority to US11/400,791 priority patent/US20060241173A1/en
Priority to US11/406,079 priority patent/US20070021624A1/en

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
    • C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
    • C07D311/26—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3
    • C07D311/28—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 2 only
    • C07D311/30—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 2 only not hydrogenated in the hetero ring, e.g. flavones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
    • A61P5/32—Antioestrogens
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
    • C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
    • C07D311/26—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3
    • C07D311/28—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 2 only
    • C07D311/32—2,3-Dihydro derivatives, e.g. flavanones
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
    • C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
    • C07D311/26—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3
    • C07D311/34—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 3 only
    • C07D311/36—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 3 only not hydrogenated in the hetero ring, e.g. isoflavones

Definitions

  • the present invention relates to a compound
  • the present invention relates to a pharmaceutical composition
  • a pharmaceutical composition comprising the compound
  • breast and endomet ⁇ al cancers are major causes of death in Western women
  • rumours in endocrine-dependent tissues, such as the breast and endomet ⁇ um occur most frequently in postmenopausal women at a time when the ovaries have ceased their production of oestrogens
  • oestrogens are the major mitogens involved in stimulating and promoting the growth ot tumours in endocrine-dependent tissues, such as the breast and endomet ⁇ um 21
  • plasma oestrogen concentrations are similar in women with or without breast cancer, breast tumour oestrone and oestradiol levels are significantly higher than in normal breast tissue or blood
  • breast tumour oestrone and oestradiol levels are significantly higher than in normal breast tissue or blood
  • oestrogens continue to be produced by extraglanduiar production in adipose tissue but also in normal and malignant breast tissues.
  • Figures 1 and 2 are schematic diagrams showing some of the enzymes involved in the tn situ synthesis of oestrone from oestrone sulphate, oestradiol and androstenedione
  • the ma two enzymes that are involved in the peripheral synthesis of oestrogens are the aromatase enzyme and the enzyme oestrone sulphatase
  • the aromatase enzyme converts androstenedione, which is secreted in large amounts by the adrenal cortex, to oestrone
  • some flavones could inhibit aromatase activity- 15 J6
  • EIS oestrone sulphate
  • PCT/GB92/01587 teaches novel steroid sulphatase inhibitors and pharmaceutical compositions containing them for use in the treatment of oestrone dependent rumours, especially breast cancer
  • These steroid sulphatase inhibitors are sulphamate esters such as N.N-dimethyl oestrone-3-sulphamate and, preferably, oestrone-3-sulphamate (otherwise known as "EM ATE”)
  • EMATE is a potent El -STS inhibitor as it displays more than 99% inhibition of El - STS activity in intact MCF-7 ceils at 0 1 ⁇ M EMATE also inhibits the El-STS enzyme in a time-dependent and concentration-dependent manner, thereby indicating that it acts as an active site-directed inactivator 7 3
  • DHA-STS dehydroepiandrosterone sulphatase
  • EMATE is also active in vivo as almost complete inhibition of rat ver El-STS (99%) and DHA-STS (99%) activities resulted when it is administered either orally or subcutaneously"
  • EMATE has been shown to have a memory enhancing effect in rats' 4
  • Studies in mice have suggested an association between DHA-STS activity and the regulation of part of the immune response. It is thought that this may also occur in humans' 5 16 .
  • EMATE is a potent steroid sulphatase inhibitor which blocks the hydrolysis of both EIS and DHA-S 29'31 This inhibitor, therefore, not only blocks the synthesis of oestrone from EIS but also the formation of androstenediol from DHA-S
  • the other major steroid with oesirogemc properties which is produced by postmenopausal women is androstenediol (see Figure 2) Androstenediol, although an androgen, can bind to the oestrogen receptor (ER) and can stimulate the growth ot ER positive breast cancer cells and the growth of carcinogen-induced mammary tumours in the rat 26 27
  • ER oestrogen receptor
  • ER oestrogen receptor
  • 90% of the androstenediol produced originates from the androgen dehydroepiandrosterone sulphate (DHA-S) which is secreted in large amounts by the adrenal cortex
  • DHA-S is convened to DHA by DHA sulphatase, which may be the same as, or different from, the enzyme, oestrone sulphatase, which is responsible for the hydrolysis of EIS 28
  • the present invention therefore seeks to overcome one or more of the problems associated with the prior art methods of treating breast and endometnal cancers _)
  • a sulphamate compound suitable for use as an inhibitor of both oestrone sulphatase activity and aromatase activity
  • the compound of the present invention is a non- steroidal compound.
  • a compound having the general formula II wherein F represents a phenolic ring structure (a first ring structure), J represents a third ring structure, I represents a phenolic ring structure (a second ring structure), G is an optional double bond, H is a link joining the second ring structure to the third ring structure, and Y represents a suitable second group, wherein any one of ring structures F, J and I has bound thereto a sulphamate group.
  • a compound according to the present invention for use as a pharmaceutical.
  • a compound according to the present invention for inhibiting oestrone sulphatase activity and aromatase activity.
  • a pharmaceutical composition comprising a compound according to the present invention, and a pharmaceutically acceptable carrier, excipient or diluent.
  • a Drocess tor preparing a compound according to the present invention, the process comprising sulphating a flavone, isofiavone or a flavanone
  • a process for preparing a compound according to the present invention comprising sulphamoylating a flavone, isofiavone or a flavanone
  • the present invention provides a compound, or a pharmaceutical composition comprising the same, that can affect, such as substantially inhibit, not only the oestrone sulphatase pathway - which pathway converts oestrone to and from oestradiol - but also the aromatase pathway - which pathway converts the androgen precursor androstenedione to oestrone
  • the present invention is further advantageous in that it may also be possible to block the formation of androstenediol from DHA-S
  • the present invention provides compounds that have considerable therapeutic advantages, particularly for treating breast and endometnal cancers
  • the compounds of the present invention are different from those disclosed in the prior art because they can act as therapeutic agents that possess both aromatase and steroid sulphatase inhibitory properties
  • the compound of the present invention compnses a first ring structure and a sulphamoyl group, which first ring structure may be substituted and/or unsaturated.
  • the first ring structure is a phenolic ring structure, which phenolic ring mav be substituted.
  • the compound of the present invention further comprises a second ring structure, which second ring structure may be substituted and/or unsaturated.
  • the second ring structure is a phenolic ring structure, which phenolic ring may be substituted.
  • the compound of the present invention further comprises a third ring structure which is intermediate the first ring structure and the second ring structure, which third ring structure may be substituted and/or unsaturated.
  • the compound of the present invention is a sulphamate of a flavone, an isofiavone or a flavanone.
  • the compound of the present invention is a sulphamate of a benzoflavone - such as the benzoflavone of Figure 10 wherein R is H or OH (ref. 38).
  • the present invention also covers substituted variants of the sulphamate of the benzoflavone of Figure 10.
  • the compound of the present invention has the general formula I wherein A represents the first ring structure, B represents the third ring structure, D represents the second ring structure, C is an optional double bond, E is a link joining the second ring structure to the third ring strucmre, X represents a suitable first group, and Y represents a suitable second group; wherein any one of ring structures A, B and D is a phenolic ring; and wherein any one of ring structures A, B and D has bound thereto a sulphamate group
  • Each of the ring structures can independently comprise from 3 to 20 atoms in the ring, preferably from 4 to 8 atoms in the ring.
  • ring A and ring D comprise 6 atoms in the ring.
  • a further cyclic group may be linked to ring A or D.
  • This cyclic group may be linked to two spaced-apart atoms in ring A or ring D, such as the structure shown in figure 10.
  • the first ring strucmre and the second ring strucmre are substituted.
  • any one of ring structures A and D has bound thereto a sulphamate group.
  • each of the first ring and the second ring is a homogeneous ring strucmre - i.e. the ring is made up of the same atoms.
  • each of the first ring and the second ring comprises only carbon atoms in the ring.
  • the compound of the present invention has the general formula II wherein F represents a phenolic ring structure (the first ring structure), J represents the third ring structure. I represents a phenolic ring strucmre (the second ring structure), G is an optional double bond, H is a link joining the second ring structure to the third ring structure, and Y represents a suitable second group; wherein any one of ring structures F, J and I has bound thereto a sulphamate group
  • the third ring structure is a heterogeneous ring structure - I e different atoms are in the ring.
  • Y is O
  • any one of the ring structures F and I has bound thereto a sulphamate group
  • link E or link H is a bond
  • the compound of the present invention is a sulphamate ot any one of a flavone, an isofiavone or a flavanone
  • the compound of the present invention is any one of a compound of the general formula IV, a compound of the general formula V, or a compound of the general formula VI; wherem R t -R ⁇ 2 are independently selected from H, OH, a halogen, an amme, an amide, a sulphonamme, a sulphonamide, any other sulphur containing group, a samrated or unsaturated C, t0 alkyl, an aryl group, a saturated or unsaturated C,. 10 ether, a saturated or unsamrated C,. l0 ester, a phosphorus containing group: and wherein at least one of R,- i 2 1S a sulphamate group.
  • the sulphamate group has the general formula OSO NR ⁇ R 14 wherein R 13 and R
  • 4 are independently selected from H, OH, a halogen, a samrated or unsamrated C
  • R !3 and R may be other suitable groups.
  • the compound of the present invention is any one of a compound of the general formula IV, a compound of the general formula V, or a compound of the general formula VI; wherein R]-R I2 are independently selected from H, OH, OSO 2 NR 13 R
  • At least one of R I3 and R is H.
  • each of R 13 and R 14 is H.
  • the compound of the present invention is a sulphamate of any one of the flavone of formula VII, the isofiavone of formula VIII, or the flavanone of formula IX.
  • the compound of the present invention is the sulphamate of any one of formula VII, formula VIII or formula IX.
  • the compound of the present invention is a sulphamate of any one of a flavone, an isofiavone or a flavanone; and wherein the sulphamoyl group is on the C4' atom of the flavone, isofiavone or flavanone.
  • the C4' position has been shown in general Formula III according to the present invention.
  • the compound of die present invention is a flavonoid or flavanoid sulphamate.
  • the present invention provides compounds that avoid the need for polytherapy.
  • the compounds of the present invention can act as therapeutic agents that possess both aromatase and steroid sulphatase inhibitory properties.
  • sulphamate group of the compound of the present invention were to be replaced with a sulphate group so as to form a sulphate compound then that sulphate compound would be hydrolysable by an enzyme having steroid sulphatase (E.C. 3.1.6.2) activity.
  • the compound of the present invention may have one or more sulphamate groups.
  • the compound may be a mono-sulphamate or a bis-sulphamate.
  • R 3 and R may be each a sulphamate.
  • Figures 1 and 2 present schematic pathways; Figure 3-10 present chemical formulae; and Figure 11 presents a graph.
  • the sulphamate derivatives were prepared essentially as described previously 29
  • a solution of the appropriate flavone, isofiavone or flavanone in anhydrous DMF was treated with sodium hydride (60% dispersion; 1 equiv for 2 and 4; 2 equiv for 6, 8 and 10) at 0°C under an atmosphere of N 2
  • sodium hydride (60% dispersion; 1 equiv for 2 and 4; 2 equiv for 6, 8 and 10) at 0°C under an atmosphere of N 2
  • sulfamoyl chloride (2 equiv except for 8, 5 equiv) was added and the reaction mixture was poured into brine after warming to room temperature overnight and diluting with ethyl acetate.
  • the organic fraction was washed exhaustively with brine, dried (MgS0 4 ), filtered and evaporated
  • the crude product obtained was purified by flash chromatography and recrystalhsation to give the corresponding sulfamate.
  • 6-Hydroxyflavone (1.0 g, 4.113 mmol) gave crude product (1 21 g) which was fractionated on silica (200 g) with ethyl acetate. Upon evaporation, the first fraction gave a creamy residue (760 mg, 58.2%) which was recrystaliised in warm acetone/hexane (3:2) to give 2 as creamy rod-shaped crystals (557 mg), m.p.
  • Sulphatase inhibition was assessed using placental microsome (100,000 g) preparations or intact MCF-7 breast cancer cells as described previously 29,3 °. Placental microsomes were incubated with 3 H EIS, adjusted to 20 ⁇ M with unlabelled substrate, in the absence or presence of inhibitor.
  • Placental microsomes were also used to assess the aromatase inhibitory properties of the flavanoid sulphamates using a tritiated water release assay 37 . Further placental microsomes (200 ⁇ l) were incubated with [ 10- _T] androstenedione, 60 nM and 1 mM NADPH in the absence or presence of inhibitor.
  • Figure 11 presents in vivo inhibition of oestrone sulphatase activity in rat liver for two isoflavones according to die present invention.
  • BH22F1 5-hydroxy isoflavone-4',7-bissulphamate
  • BH22BF1 5,7-dihydroxy isoflavone-4' -sulphamate.

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  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Endocrinology (AREA)
  • Diabetes (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Pyridine Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Macromolecular Compounds Obtained By Forming Nitrogen-Containing Linkages In General (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Pyrane Compounds (AREA)

Abstract

Cette invention concerne un composé sulfamate. Ce composé peut être utilisé en tant qu'inhibiteur à la fois d'une activité de sulfatase de l'oestrone et d'une activité d'aromatase. Un composé préféré est représenté par la formule (II) dans laquelle F représente une structure cyclique phénolique (la première structure cyclique), J représente la troisième structure cyclique, I représente une structure cyclique phénolique (la deuxième structure cyclique), G est une double liaison facultative, H est une liaison entre la deuxième structure cyclique et la troisième structure cyclique, et Y représente un second groupe approprié, l'une ou l'autre de ces structures cycliques F, J et I étant liée à un groupe sulfamate.
PCT/GB1997/000600 1991-08-28 1997-03-04 Composes comportant un groupe sulfamate WO1997032872A1 (fr)

Priority Applications (16)

Application Number Priority Date Filing Date Title
US09/142,194 US6083978A (en) 1996-03-05 1997-03-04 Compounds with a sulfamate group
AT97905332T ATE286038T1 (de) 1996-03-05 1997-03-04 Verbindungen mit sulfonsäure-amidgruppe
DE69732098T DE69732098T2 (de) 1996-03-05 1997-03-04 Verbindungen mit sulfonsäure-amidgruppe
AU22255/97A AU2225597A (en) 1996-03-05 1997-03-04 Compounds with a sulfamate group
JP9531567A JP2000506161A (ja) 1996-03-05 1997-03-04 スルファメート基を有する化合物
EP97905332A EP0885211B1 (fr) 1996-03-05 1997-03-04 Composes comportant un groupe sulfamate
US09/193,970 US6476011B1 (en) 1991-08-28 1998-11-18 Methods for introducing an estrogenic compound
US09/238,345 US6187766B1 (en) 1991-08-28 1999-01-27 Steroid sulphatase inhibitors
US09/579,163 US6642397B1 (en) 1991-08-28 2000-05-25 Steroid sulphatase inhibitors
US09/638,315 US6506792B1 (en) 1997-03-04 2000-08-14 Compounds that inhibit oestrone sulphatase and/or aromatase and methods for making and using
US09/794,853 US6903084B2 (en) 1991-08-28 2001-02-27 Steroid sulphatase inhibitors
US10/082,007 US6677325B2 (en) 1991-08-28 2002-02-21 Steroid sulphatase inhibitors
US10/084,235 US7098199B2 (en) 1991-08-29 2002-02-25 Steroid sulphatase inhibitors
US10/327,500 US7129269B2 (en) 1996-03-05 2002-12-20 Compound
US11/400,791 US20060241173A1 (en) 1996-02-16 2006-04-07 Compound
US11/406,079 US20070021624A1 (en) 1991-08-29 2006-04-18 Steroid sulphatase inhibitors

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
GBGB9604709.7A GB9604709D0 (en) 1996-03-05 1996-03-05 A compound
GBGB9605725.2A GB9605725D0 (en) 1996-03-05 1996-03-19 A compound
GB9604709.7 1996-03-19
GB9605725.2 1996-03-19

Related Parent Applications (2)

Application Number Title Priority Date Filing Date
PCT/GB1997/000444 Continuation-In-Part WO1997030041A1 (fr) 1991-08-28 1997-02-17 Derives du type sulfamate non steroidiens a noyau polycyclique, leur preparation et leur utilisation comme inhibiteurs de l'oestrone sulfatase
GBPCT/GB97/004444 Continuation-In-Part 1997-02-17

Related Child Applications (7)

Application Number Title Priority Date Filing Date
US08196192 Continuation-In-Part 1992-08-28
PCT/GB1992/001587 Continuation-In-Part WO1993005064A1 (fr) 1991-08-28 1992-08-28 Inhibiteurs de sulfatase steroidienne
US08/196,192 Continuation-In-Part US5616574A (en) 1991-08-28 1992-08-28 Steroid sulphatase inhibitors
US14219493A Continuation-In-Part 1991-03-05 1993-10-22
PCT/GB1997/003352 Continuation-In-Part WO1998024802A2 (fr) 1991-08-28 1997-12-04 Compose
US09/111,927 Continuation-In-Part US6011024A (en) 1991-08-28 1998-07-08 Steroid sulphatase inhibitors
US10/082,007 Continuation-In-Part US6677325B2 (en) 1991-08-28 2002-02-21 Steroid sulphatase inhibitors

Publications (1)

Publication Number Publication Date
WO1997032872A1 true WO1997032872A1 (fr) 1997-09-12

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB1997/000600 WO1997032872A1 (fr) 1991-08-28 1997-03-04 Composes comportant un groupe sulfamate

Country Status (8)

Country Link
US (1) US6083978A (fr)
EP (1) EP0885211B1 (fr)
JP (1) JP2000506161A (fr)
AT (1) ATE286038T1 (fr)
AU (1) AU2225597A (fr)
DE (1) DE69732098T2 (fr)
ES (1) ES2233998T3 (fr)
WO (1) WO1997032872A1 (fr)

Cited By (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999027935A1 (fr) * 1997-12-04 1999-06-10 Sterix Limited Derives de 3-o-sulfamate steroide utilises comme inhibiteurs de l'oestrone-sulfatase
WO1999052890A1 (fr) * 1998-04-09 1999-10-21 Novartis Ag Derives de chromanone et de thiochromanone
US6159960A (en) * 1991-08-28 2000-12-12 Sterix Limited Steroid sulphatase inhibitors
WO2001002349A1 (fr) * 1999-07-06 2001-01-11 Teikoku Hormone Mfg. Co., Ltd. Derives phenyl-sulfamates
WO2001004086A1 (fr) * 1999-07-09 2001-01-18 Btg International Limited Composes de sulphamate
US6187766B1 (en) 1991-08-28 2001-02-13 Imperial College Of Science Technology & Medicine Steroid sulphatase inhibitors
US6239169B1 (en) 1996-02-16 2001-05-29 Sterix Limited Non-steroidal polycyclic ring sulphamate derivatives, their preparation and their use as oestrone sulphatase inhibitors
US6262043B1 (en) 1999-04-13 2001-07-17 Kyowa Hakko Kogyo Co., Ltd. Estra-1,3,5(10),16-tetraene derivatives
US6476011B1 (en) 1991-08-28 2002-11-05 Sterix Limited Methods for introducing an estrogenic compound
WO2002081491A3 (fr) * 2001-04-09 2004-02-26 Inst Farmaceutyczny Nouveaux derives de genisteine et preparations pharmaceutiques les contenant
US6903084B2 (en) 1991-08-28 2005-06-07 Sterix Limited Steroid sulphatase inhibitors
US6921776B1 (en) 1996-02-16 2005-07-26 Sterix Limited Compound
US7078395B1 (en) 1999-06-16 2006-07-18 Sterix Limited Methods for treating or preventing cancer by preventing, inhibiting or arresting cell cycling
US7335650B2 (en) 2000-01-14 2008-02-26 Sterix Limited Composition
US7745472B2 (en) 2001-11-21 2010-06-29 Sterix Limited Compound
WO2011100433A1 (fr) 2010-02-12 2011-08-18 N30 Pharmaceuticals, Llc Inhibiteurs inédits de la s-nitrosoglutathione réductase
US8207152B2 (en) 1999-04-30 2012-06-26 Sterix Limited Methods for treating or preventing cancer by preventing, inhibiting, or arresting cell cycling
US8669381B2 (en) 2010-02-12 2014-03-11 N30 Pharmaceuticals, Inc. Chromone inhibitors of S-nitrosoglutathione reductase

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040127473A1 (en) * 1996-12-05 2004-07-01 Reed Michael John Compound
GB2331987B (en) * 1997-12-04 2002-11-27 Imperial College Polycyclic sulphamate inhibitors of oestrone sulphatase
WO1999035138A1 (fr) * 1998-01-12 1999-07-15 Nichimo Kabushiki Kaisha Procede de preparation de composes d'isoflavone
MXPA04002077A (es) * 2001-09-06 2005-02-17 Synorx Inc Inhibicion por 3-doxiflavonoides de actividad de t-linfocitos y terapias relacionadas.
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ATE286038T1 (de) 2005-01-15
US6083978A (en) 2000-07-04
DE69732098D1 (de) 2005-02-03
AU2225597A (en) 1997-09-22
ES2233998T3 (es) 2005-06-16
EP0885211B1 (fr) 2004-12-29
EP0885211A1 (fr) 1998-12-23
DE69732098T2 (de) 2005-12-08
JP2000506161A (ja) 2000-05-23

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